Crystal structure of 2-amino-7-hy­droxy-4-(4-hy­droxy­phen­yl)-4H-chromene-3-carbo­nitrile

In the title compound, C₁₆H₁₂N₂O₃, the chromene ring system is nearly planar [maximum deviation from the mean plane = 0.057 (1) Å], and is almost perpendicular to the benzene ring, with a dihedral angle of 85.29 (5)°. In the crystal, mol­ecules are linked by classical N—H...O, O—H...O and O—H...N hydrogen bonds, and weak C—H...O hydrogen bonds, forming a three-dimensional supra­molecular network. Furthermore, a weak π–π stacking inter­action is observed; the centroid-to-centroid distance is 3.7260 (7) Å.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.034
• wR factor = 0.091
• Data-to-parameter ratio = 14.5

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600          3 Report

Alert level G
PLAT002_ALERT_2_G Number of Distance or Angle Restraints on AtSite          7 Note
PLAT172_ALERT_4_G The CIF-Embedded .res File Contains DFIX Records          2 Report
PLAT230_ALERT_2_G Hirshfeld Test Diff for    C2     --  C10     ..        7.0 su
PLAT793_ALERT_4_G The Model has Chirality at C3      (Centro SPGR)          R Verify
PLAT860_ALERT_3_G Number of Least-Squares Restraints .............          4 Note
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Th(Min) ...          3 Report

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   1 ALERT level C = Check. Ensure it is not caused by an omission or oversight
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   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
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S1. Comment

Heterocycles containing the chromene moiety show interesting biological activities such as antitumor (Mohr et al., 1975), sex pheromone (Bianchi & Tava, 1987), antimicrobial (Khafagy et al., 2002), and mutagenicity (Hiramoto et al., 1997). Interestingly, 2-amino-4H-chromene derivatives arises from their potential application in the treatment of human inflammatory TNFa-mediated diseases, such as psoriatic arthritis and rheumatoid and in cancer therapy (Skommer et al., 2006; Gourdeau et al., 2004; Anderson et al., 2005; Wang et al., 2000). Such facts inspired us to synthesize and determine the crystal structure of the title compound in this study.

As shown in Fig. 1, the 4H-chromene ring system (O1/C1–C9) of the title compound is almost planar with the puckering parameters of Q(2) = 0.0759 (12) Å and φ(2) = 155.5 (9) °. It makes a dihedral angle of 85.29 (5)° with the C11–C16 phenyl ring.

In the crystal structure, N—H···O, O—H···O, O—H···N and C—H···O hydrogen bonds link the adjacent molecules, forming the three dimensional network (Table 1, Fig. 2). In addition, a weak π-π stacking interaction [Cg1···Cg1 = 3.7260 (7) Å]; where Cg1 is the centroid of the O1/C1–C4/C9 ring of the 4H-chromene ring system (O1/C1–C9)] are observed.

Related literature

For the synthesis and biological activity of molecules having the 2-amino-7-hydroxy-4-(4-hydroxyphenyl)-4H-chromene unit, see: Mohr et al. (1975); Bianchi & Tava (1987); Khafagy et al. (2002); Hiramoto et al. (1997); Skommer et al. (2006); Gourdeau et al. (2004); Anderson et al. (2005); Wang et al. (2000).

S2. Experimental

A mixture of 1 mmol (180 mg) of 4-hydroxybenzylidene-malononitrile and 1 mmol (110 mg) of resorcinol was refluxed in 10 ml e thanol for 3 h in the presence of few catalytic drops of pipredine. The mixture was cooled at ambient temperature and the resulting solid was filtered off, dried under vacuum and recrytallized from ethanol to furnish white crystals in a good quality suitable for X-ray diffraction. Mp 523 K.

S3. Refinement

The H atoms of the OH and NH₂ groups were located in a difference Fourier map and were refined freely [O2—H2O = 0.893 (17) Å, O3—H3O = 0.866 (14) Å, N1—H1N = 0.881 (13) Å and N1—H2N = 0.895 (17) Å]. The H atoms attached to the C atoms were positioned geometrically, with C—H = 0.95 Å and C—H = 1.00 Å for aromatic and methine H, respectively and H atoms were constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C).

Computing details

Data collection: CrystalClear-SM (Rigaku, 2012); cell refinement: CrystalClear-SM (Rigaku, 2012); data reduction: CrystalClear-SM (Rigaku, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012).

Figures

	Fig. 1. View of the title compound with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level.
	Fig. 2. The packing diagram of the title compound viewed down the b axis.

2-Amino-7-hydroxy-4-(4-hydroxyphenyl)-4H-chromene-3-carbonitrile

Crystal data

C16H12N2O3	F(000) = 1168
Mr = 280.28	Dx = 1.423 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71075 Å
Hall symbol: -C 2yc	Cell parameters from 14157 reflections
a = 18.3084 (13) Å	θ = 2.3–27.5°
b = 6.0743 (4) Å	µ = 0.10 mm^−1
c = 24.5339 (17) Å	T = 100 K
β = 106.471 (2)°	Blade, brown
V = 2616.5 (3) Å^3	0.25 × 0.10 × 0.03 mm
Z = 8

Data collection

Rigaku AFC12 (Right) diffractometer	2986 independent reflections
Radiation source: Rotating Anode	2540 reflections with I > 2σ(I)
Detector resolution: 28.5714 pixels mm^-1	Rint = 0.032
profile data from ω–scans	θmax = 27.5°, θmin = 3.3°
Absorption correction: multi-scan (CrystalClear-SM; Rigaku, 2012)	h = −23→18
Tmin = 0.830, Tmax = 1.000	k = −7→7
13649 measured reflections	l = −31→31

Refinement

Refinement on F^2	4 restraints
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.091	w = 1/[σ^2(Fo^2) + (0.0397P)^2 + 1.7337P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max < 0.001
2986 reflections	Δρmax = 0.28 e Å^−3
206 parameters	Δρmin = −0.20 e Å^−3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.05989 (4)	0.30160 (13)	0.03455 (3)	0.0187 (2)
O2	−0.15605 (5)	−0.03145 (14)	0.06613 (4)	0.0226 (3)
O3	0.20866 (5)	0.79736 (15)	0.35127 (3)	0.0213 (3)
N1	0.16338 (6)	0.41872 (18)	0.01319 (4)	0.0207 (3)
N2	0.21498 (6)	0.93998 (18)	0.09021 (5)	0.0268 (3)
C1	0.11540 (6)	0.45728 (19)	0.04464 (5)	0.0173 (3)
C2	0.11794 (6)	0.62821 (19)	0.08107 (5)	0.0178 (3)
C3	0.06229 (6)	0.66058 (19)	0.11588 (5)	0.0174 (3)
C4	0.00672 (6)	0.46994 (19)	0.10543 (5)	0.0170 (3)
C5	−0.04921 (6)	0.4552 (2)	0.13396 (5)	0.0192 (3)
C6	−0.10354 (6)	0.2906 (2)	0.12215 (5)	0.0196 (3)
C7	−0.10248 (6)	0.13336 (19)	0.08098 (5)	0.0180 (3)
C8	−0.04727 (6)	0.14161 (19)	0.05235 (5)	0.0172 (3)
C9	0.00636 (6)	0.30919 (19)	0.06543 (5)	0.0164 (3)
C10	0.17293 (7)	0.7951 (2)	0.08532 (5)	0.0200 (3)
C11	0.10251 (6)	0.69419 (19)	0.17886 (5)	0.0178 (3)
C12	0.08736 (7)	0.8801 (2)	0.20677 (5)	0.0235 (3)
C13	0.12262 (7)	0.9120 (2)	0.26446 (5)	0.0250 (3)
C14	0.17396 (6)	0.7573 (2)	0.29446 (5)	0.0182 (3)
C15	0.19056 (7)	0.5711 (2)	0.26720 (5)	0.0206 (3)
C16	0.15444 (7)	0.5408 (2)	0.20975 (5)	0.0210 (3)
H1N	0.1546 (9)	0.304 (2)	−0.0097 (6)	0.034 (4)*
H2N	0.2042 (8)	0.505 (3)	0.0173 (7)	0.034 (4)*
H2O	−0.1713 (10)	−0.071 (3)	0.0962 (7)	0.049 (5)*
H3	0.03240	0.79710	0.10170	0.0210*
H3O	0.2327 (9)	0.681 (2)	0.3673 (7)	0.040 (5)*
H5	−0.04990	0.56130	0.16230	0.0230*
H6	−0.14130	0.28470	0.14190	0.0240*
H8	−0.04620	0.03470	0.02430	0.0210*
H12	0.05240	0.98710	0.18620	0.0280*
H13	0.11150	1.03930	0.28310	0.0300*
H15	0.22620	0.46570	0.28770	0.0250*
H16	0.16540	0.41290	0.19120	0.0250*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0184 (4)	0.0189 (4)	0.0203 (4)	−0.0043 (3)	0.0080 (3)	−0.0035 (3)
O2	0.0241 (4)	0.0258 (5)	0.0199 (4)	−0.0092 (3)	0.0096 (3)	−0.0028 (3)
O3	0.0241 (4)	0.0233 (5)	0.0150 (4)	0.0059 (3)	0.0030 (3)	−0.0014 (3)
N1	0.0188 (5)	0.0219 (5)	0.0228 (5)	−0.0046 (4)	0.0081 (4)	−0.0032 (4)
N2	0.0253 (5)	0.0250 (6)	0.0279 (6)	−0.0066 (4)	0.0039 (4)	−0.0015 (4)
C1	0.0157 (5)	0.0183 (6)	0.0164 (5)	−0.0015 (4)	0.0019 (4)	0.0028 (4)
C2	0.0177 (5)	0.0186 (6)	0.0157 (5)	−0.0021 (4)	0.0026 (4)	0.0009 (4)
C3	0.0188 (5)	0.0162 (5)	0.0161 (5)	0.0007 (4)	0.0031 (4)	0.0001 (4)
C4	0.0168 (5)	0.0172 (6)	0.0153 (5)	0.0011 (4)	0.0016 (4)	0.0015 (4)
C5	0.0206 (5)	0.0203 (6)	0.0164 (5)	0.0021 (4)	0.0047 (4)	−0.0009 (4)
C6	0.0186 (5)	0.0234 (6)	0.0176 (5)	0.0013 (4)	0.0064 (4)	0.0021 (4)
C7	0.0174 (5)	0.0182 (6)	0.0173 (5)	−0.0020 (4)	0.0032 (4)	0.0024 (4)
C8	0.0192 (5)	0.0168 (5)	0.0151 (5)	0.0001 (4)	0.0040 (4)	−0.0002 (4)
C9	0.0153 (5)	0.0188 (6)	0.0149 (5)	0.0010 (4)	0.0040 (4)	0.0021 (4)
C10	0.0208 (6)	0.0212 (6)	0.0165 (5)	0.0004 (5)	0.0030 (4)	0.0000 (4)
C11	0.0176 (5)	0.0187 (6)	0.0166 (5)	−0.0017 (4)	0.0042 (4)	−0.0009 (4)
C12	0.0258 (6)	0.0205 (6)	0.0213 (6)	0.0055 (5)	0.0022 (5)	−0.0009 (5)
C13	0.0299 (6)	0.0215 (6)	0.0217 (6)	0.0065 (5)	0.0044 (5)	−0.0048 (5)
C14	0.0177 (5)	0.0213 (6)	0.0158 (5)	−0.0009 (4)	0.0052 (4)	−0.0013 (4)
C15	0.0203 (5)	0.0209 (6)	0.0194 (6)	0.0049 (4)	0.0039 (4)	0.0012 (5)
C16	0.0235 (6)	0.0191 (6)	0.0198 (6)	0.0034 (4)	0.0053 (5)	−0.0028 (4)

Geometric parameters (Å, º)

O1—C1	1.3586 (14)	C6—C7	1.3943 (17)
O1—C9	1.3992 (14)	C7—C8	1.3857 (16)
O2—C7	1.3763 (15)	C8—C9	1.3873 (16)
O3—C14	1.3796 (14)	C11—C12	1.3888 (17)
N1—C1	1.3440 (16)	C11—C16	1.3921 (17)
N2—C10	1.1529 (17)	C12—C13	1.3926 (17)
O2—H2O	0.893 (17)	C13—C14	1.3842 (17)
O3—H3O	0.866 (14)	C14—C15	1.3907 (17)
N1—H1N	0.881 (13)	C15—C16	1.3890 (17)
C1—C2	1.3622 (16)	C3—H3	1.0000
N1—H2N	0.895 (17)	C5—H5	0.9500
C2—C3	1.5164 (16)	C6—H6	0.9500
C2—C10	1.4116 (17)	C8—H8	0.9500
C3—C11	1.5252 (17)	C12—H12	0.9500
C3—C4	1.5146 (16)	C13—H13	0.9500
C4—C9	1.3831 (16)	C15—H15	0.9500
C4—C5	1.3975 (16)	C16—H16	0.9500
C5—C6	1.3819 (17)
C1—O1—C9	118.75 (9)	C3—C11—C16	121.40 (10)
C7—O2—H2O	110.1 (12)	C12—C11—C16	118.48 (11)
C14—O3—H3O	110.1 (10)	C3—C11—C12	120.12 (10)
O1—C1—N1	110.55 (10)	C11—C12—C13	120.96 (11)
C1—N1—H1N	118.2 (11)	C12—C13—C14	119.68 (11)
C1—N1—H2N	119.6 (11)	O3—C14—C13	117.79 (11)
H1N—N1—H2N	122.1 (15)	C13—C14—C15	120.29 (11)
O1—C1—C2	122.33 (10)	O3—C14—C15	121.90 (11)
N1—C1—C2	127.11 (11)	C14—C15—C16	119.32 (11)
C3—C2—C10	116.38 (10)	C11—C16—C15	121.26 (11)
C1—C2—C3	124.40 (10)	C2—C3—H3	107.00
C1—C2—C10	119.13 (11)	C4—C3—H3	107.00
C4—C3—C11	112.46 (10)	C11—C3—H3	108.00
C2—C3—C11	112.30 (10)	C4—C5—H5	119.00
C2—C3—C4	109.38 (9)	C6—C5—H5	119.00
C3—C4—C5	121.11 (10)	C5—C6—H6	120.00
C5—C4—C9	116.96 (11)	C7—C6—H6	120.00
C3—C4—C9	121.85 (10)	C7—C8—H8	121.00
C4—C5—C6	121.83 (11)	C9—C8—H8	121.00
C5—C6—C7	119.37 (11)	C11—C12—H12	120.00
O2—C7—C8	117.36 (10)	C13—C12—H12	120.00
C6—C7—C8	120.29 (11)	C12—C13—H13	120.00
O2—C7—C6	122.33 (10)	C14—C13—H13	120.00
C7—C8—C9	118.65 (11)	C14—C15—H15	120.00
O1—C9—C4	122.98 (10)	C16—C15—H15	120.00
O1—C9—C8	114.15 (10)	C11—C16—H16	119.00
C4—C9—C8	122.88 (11)	C15—C16—H16	119.00
N2—C10—C2	175.64 (14)
C9—O1—C1—N1	177.24 (9)	C5—C4—C9—O1	−178.77 (10)
C9—O1—C1—C2	−4.25 (16)	C5—C4—C9—C8	1.38 (18)
C1—O1—C9—C8	−179.32 (10)	C3—C4—C9—C8	−175.44 (11)
C1—O1—C9—C4	0.81 (16)	C3—C4—C5—C6	175.56 (11)
N1—C1—C2—C3	−179.28 (11)	C4—C5—C6—C7	0.50 (18)
N1—C1—C2—C10	4.29 (19)	C5—C6—C7—C8	0.26 (18)
O1—C1—C2—C10	−173.96 (10)	C5—C6—C7—O2	−178.29 (11)
O1—C1—C2—C3	2.47 (18)	O2—C7—C8—C9	178.43 (10)
C10—C2—C3—C4	178.86 (10)	C6—C7—C8—C9	−0.19 (18)
C1—C2—C3—C4	2.34 (16)	C7—C8—C9—C4	−0.67 (18)
C1—C2—C3—C11	127.93 (12)	C7—C8—C9—O1	179.46 (10)
C10—C2—C3—C11	−55.55 (14)	C3—C11—C12—C13	178.99 (11)
C2—C3—C4—C9	−5.55 (15)	C16—C11—C12—C13	−0.61 (19)
C11—C3—C4—C5	52.26 (15)	C3—C11—C16—C15	−179.53 (11)
C2—C3—C11—C12	124.45 (12)	C12—C11—C16—C15	0.07 (19)
C2—C3—C11—C16	−55.96 (15)	C11—C12—C13—C14	0.48 (19)
C11—C3—C4—C9	−131.05 (12)	C12—C13—C14—O3	178.81 (11)
C2—C3—C4—C5	177.75 (11)	C12—C13—C14—C15	0.21 (19)
C4—C3—C11—C16	67.94 (14)	O3—C14—C15—C16	−179.28 (11)
C4—C3—C11—C12	−111.66 (12)	C13—C14—C15—C16	−0.74 (19)
C9—C4—C5—C6	−1.29 (17)	C14—C15—C16—C11	0.60 (19)
C3—C4—C9—O1	4.41 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O2^i	0.88 (1)	2.16 (1)	3.0316 (14)	169 (2)
N1—H2N···O2^ii	0.90 (2)	2.51 (2)	3.2052 (15)	135 (1)
O2—H2O···O3^iii	0.89 (2)	1.81 (2)	2.6875 (13)	168 (2)
O3—H3O···N2^iv	0.87 (1)	1.89 (1)	2.7550 (14)	174 (2)
C8—H8···O1^i	0.95	2.47	3.4011 (14)	165

Symmetry codes: (i) −x, −y, −z; (ii) x+1/2, y+1/2, z; (iii) −x, y−1, −z+1/2; (iv) −x+1/2, y−1/2, −z+1/2.